Redecker Christoph, Wang Wei, Fritschy Jean-Marc, Witte Otto W
Department of Neurology, Friedrich-Schiller-University, Philosophenweg 3, D-07743 Jena, Germany. redecker@ med.uni-jena.de
J Cereb Blood Flow Metab. 2002 Dec;22(12):1463-75. doi: 10.1097/01.WCB.0000034149.72481.BD.
Impairment of inhibitory neurotransmission has been reported to occur in widespread, structurally intact brain regions after focal ischemic stroke. These long-lasting alterations contribute to the functional deficit and influence long-term recovery. Inhibitory neurotransmission is primarily mediated by gamma-aminobutyric acid (GABA)A receptors assembled of five subunits that allow a variety of adaptive changes. In this study, the regional distribution of five major GABA(A)-receptor subunits (alpha1, alpha2, alpha3, alpha5, and gamma2) was analyzed immunohistochemically 1, 7, and 30 days after photochemically induced cortical infarcts. When compared with sham-operated controls, a general and regionally differential reduction in immunostaining was found within the cortex, hippocampus, and thalamus of both hemispheres for almost all subunits. Within ipsilateral and contralateral neocortical areas, a specific pattern of changes with a differential decrease of subunits alpha1, alpha2, alpha5, and gamma2 and a significant upregulation of subunit alpha3 was observed in the contralateral cortex homotopic to the infarct. This dysregulation was most prominent at day 7 and still present at day 30. Interestingly, a single application of the noncompetitive N-methyl-D-aspartate-receptor antagonist MK-801 during lesion induction completely blocked these bihemispheric alterations. Cortical spreading depressions induced by topical application of KCl do not change GABA(A)-receptor subunit expression. As alterations in subtype distribution crucially influence inhibitory function, ischemia-induced modifications in GABA(A)-receptor subtype expression may be of relevance for functional recovery after stroke.
据报道，局灶性缺血性中风后，在广泛的、结构完整的脑区会出现抑制性神经传递受损的情况。这些长期变化会导致功能缺陷并影响长期恢复。抑制性神经传递主要由由五个亚基组装而成的γ-氨基丁酸（GABA）A受体介导，这些亚基允许发生各种适应性变化。在本研究中，在光化学诱导的皮质梗死1天、7天和30天后，通过免疫组织化学分析了五种主要GABA（A）受体亚基（α1、α2、α3、α5和γ2）的区域分布。与假手术对照组相比，几乎所有亚基在双侧大脑半球的皮质、海马体和丘脑中均发现免疫染色普遍且存在区域差异的减少。在同侧和对侧新皮质区域，在梗死灶同侧的对侧皮质中观察到一种特定的变化模式，即亚基α1、α2、α5和γ2差异性减少，而亚基α3显著上调。这种失调在第7天最为明显，在第30天仍然存在。有趣的是，在损伤诱导期间单次应用非竞争性N-甲基-D-天冬氨酸受体拮抗剂MK-801可完全阻断这些双侧半球的变化。局部应用氯化钾诱导的皮质扩散性抑制不会改变GABA（A）受体亚基的表达。由于亚型分布的改变对抑制功能至关重要，缺血诱导的GABA（A）受体亚型表达的改变可能与中风后的功能恢复有关。
